The RUSH2A Study: Best-Corrected Visual Acuity, Full-Field Electroretinography Amplitudes, and Full-Field Stimulus Thresholds at Baseline

David G Birch; Peiyao Cheng; Jacque L Duncan; Allison R Ayala; Maureen G Maguire; Isabelle Audo; Janet K Cheetham; Todd A Durham; Abigail T Fahim; Frederick L Ferris 3rd; Elise Heon; Rachel M Huckfeldt; Alessandro Iannaccone; Naheed W Khan; Eleonora M Lad; Michel Michaelides; Mark E Pennesi; Katarina Stingl; Ajoy Vincent; Christina Y Weng; Foundation Fighting Blindness Consortium Investigator Group

doi:10.1167/tvst.9.11.9

The RUSH2A Study: Best-Corrected Visual Acuity, Full-Field Electroretinography Amplitudes, and Full-Field Stimulus Thresholds at Baseline

Transl Vis Sci Technol. 2020 Oct 8;9(11):9. doi: 10.1167/tvst.9.11.9. eCollection 2020 Oct.

Authors

David G Birch¹, Peiyao Cheng², Jacque L Duncan³, Allison R Ayala², Maureen G Maguire⁴, Isabelle Audo^{5

6}, Janet K Cheetham⁷, Todd A Durham⁷, Abigail T Fahim⁸, Frederick L Ferris 3rd⁹, Elise Heon¹⁰, Rachel M Huckfeldt¹¹, Alessandro Iannaccone¹², Naheed W Khan⁸, Eleonora M Lad¹², Michel Michaelides¹³, Mark E Pennesi¹⁴, Katarina Stingl^{15

16}, Ajoy Vincent¹⁰, Christina Y Weng¹⁷; Foundation Fighting Blindness Consortium Investigator Group

Affiliations

¹ Retina Foundation of the Southwest, Dallas, TX, USA.
² Jaeb Center for Health Research, Tampa, FL, USA.
³ University of California, San Francisco, San Francisco, CA, USA.
⁴ University of Pennsylvania, Philadelphia, PA, USA.
⁵ Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France.
⁶ Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM-DGOS CIC1423, Paris, France.
⁷ Foundation Fighting Blindness, Columbia, MD, USA.
⁸ University of Michigan, Kellogg Eye Center, Ann Arbor, MI, USA.
⁹ Ophthalmic Research Consultants, Waxhaw, NC, USA.
¹⁰ Departments of Ophthalmology and Vision Sciences, The Hospital for Sick Children, The University of Toronto, Toronto, Ontario, Canada.
¹¹ Massachusetts Eye and Ear, Boston, MA, USA.
¹² Duke University Medical Center, Department of Ophthalmology, Durham, NC, USA.
¹³ Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK.
¹⁴ Casey Eye Institute - Oregon Health & Science University, Portland, OR, USA.
¹⁵ University Eye Hospital, Center for Ophthalmology, University of Tuebingen, Tuebingen, Germany.
¹⁶ Center for Rare Eye Diseases, University of Tuebingen, Tuebingen, Germany.
¹⁷ Baylor College of Medicine, Houston, TX, USA.

Abstract

Purpose: The purpose of this study was to evaluate baseline best corrected visual acuity (BCVA), full-field electroretinography (ERG), full-field stimulus thresholds (FST), and their relationship with baseline demographic and clinical characteristics in the Rate of Progression in Usher syndrome type 2 (USH2A)-related Retinal Degeneration (RUSH2A) multicenter study.

Methods: Participants had Usher syndrome type 2 (USH2, N = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP, N = 47) associated with biallelic variants in the USH2A gene. Associations of demographic and clinical characteristics with BCVA, ERG, and FST were assessed with regression models.

Results: In comparison to ARRP, USH2 had worse BCVA (median 79 vs. 82 letters; P < 0.001 adjusted for age), lower rod-mediated ERG b-wave amplitudes (median 0.0 vs. 6.6 µV; P < 0.001) and 30 Hz flicker cone-mediated ERG amplitudes (median 1.5 vs. 3.1 µV; P = 0.001), and higher (white, blue, and red) FST thresholds (means [-26, -31, -23 dB] vs. [-39, -45, -28 dB]; P < 0.001 for all stimuli). After adjusting for age, gender, and duration of vision loss, the difference in BCVA between diagnosis groups was attenuated (P = 0.09). Only diagnosis was associated with rod- and cone-mediated ERG parameters, whereas both genders (P = 0.04) and duration of visual loss (P < 0.001) also were associated with FST white stimulus.

Conclusions: USH2 participants had worse BCVA, ERG, and FST than ARRP participants. FST was strongly associated with duration of disease; it remains to be determined whether it will be a sensitive measure of progression.

Translational relevance: Using standardized research protocols in RUSH2A, measures have been identified to monitor disease progression and treatment response and differentiate features of prognostic relevance between USH2 and ARRP participants with USH2A mutations.

Keywords: Usher syndrome type 2 (USH2A); best corrected visual acuity (BCVA); electroretinography (ERG); full-field stimulus test; retinitis pigmentosa.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Electroretinography
Female
Humans
Male
Retinitis Pigmentosa*
Usher Syndromes*
Visual Acuity
Visual Fields

Abstract

Publication types

MeSH terms

Grants and funding